The effect of two frequent amino acid variants of the hepatocyte nuclear factor-1α gene on estimates of the pancreatic β-cell function in Caucasian glucosetolerant first-degree relatives of type 2 diabetic patients

Søren A. Urhammer; Ann Merete Møller; Birgit Nyholm; Claus T. Ekstrøm; Hans Eiberg; Jesper O. Clausen; Torben Hansen; Oluf Pedersen; Ole Schmitz

The effect of two frequent amino acid variants of the hepatocyte nuclear factor-1α gene on estimates of the pancreatic β-cell function in Caucasian glucosetolerant first-degree relatives of type 2 diabetic patients

Søren A. Urhammer^*, Ann Merete Møller, Birgit Nyholm, Claus T. Ekstrøm, Hans Eiberg, Jesper O. Clausen, Torben Hansen, Oluf Pedersen, Ole Schmitz

^*Corresponding author for this work

14 Citations (Scopus)

Abstract

The objective of the present study was to investigate whether the frequent amino acid polymorphisms, Ile/Leu27 and Ser/Asn487, of the hepatocyte nuclear factor-1α gene were associated with alterations in glucose-induced serum C-peptide and serum insulin responses among glucose- tolerant first-degree relatives of type 2 diabetic patients. The study comprised 2 independent Danish cohorts. Among 74 unrelated type 2 diabetic relatives, 12 homozygous carriers of the Ile/Leu27 polymorphism had a 32% decrease in the 30-min serum C-peptide level (P = 0.01), as well as a 39% decrease in the 30-min serum insulin level (P = 0.02) during an oral glucose tolerance test. Ten homozygous carriers of the Ile/Leu27 variant did, however, not differ from wildtype carriers, with respect to the acute circulating insulin and serum C-peptide responses during an iv glucose tolerance test in the same study cohort. In a larger (more than 3-fold) study group of 230 glucose tolerant offspring of 62 type 2 diabetic probands, 33 homozygous carriers of the Ile/Leu27 variant did not differ, with respect to either serum insulin and serum C-peptide levels during an oral glucose tolerance test or acute serum insulin and serum C-peptide responses during an iv glucose tolerance test. We therefore consider the former positive finding as a statistical type I error. There were no differences in the above mentioned variables between carriers of the Ser/Asn487 polymorphism and wild- type carriers within any of the 2 study populations. Nor did carriers of combined genotypes, i.e. carriers of both the Ile/Leu27 and the Ser/Asn487 variants, show any associations with the examined variables. In conclusion, the Ile/Leu27 and Set/Ash487 polymorphisms of the hepatocyte nuclear factor- 1α gene have apparently no major impact on the pancreatic β-cell function, after an oral and iv glucose challenge, in Caucasian first-degree relatives of type 2 diabetic patients.

Original language	English
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	83
Issue number	11
Pages (from-to)	3992-3995
Number of pages	4
ISSN	0021-972X
Publication status	Published - 20 Nov 1998

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Urhammer, S. A., Møller, A. M., Nyholm, B., Ekstrøm, C. T., Eiberg, H., Clausen, J. O., Hansen, T., Pedersen, O., & Schmitz, O. (1998). The effect of two frequent amino acid variants of the hepatocyte nuclear factor-1α gene on estimates of the pancreatic β-cell function in Caucasian glucosetolerant first-degree relatives of type 2 diabetic patients. Journal of Clinical Endocrinology and Metabolism, 83(11), 3992-3995.

The effect of two frequent amino acid variants of the hepatocyte nuclear factor-1α gene on estimates of the pancreatic β-cell function in Caucasian glucosetolerant first-degree relatives of type 2 diabetic patients. / Urhammer, Søren A.; Møller, Ann Merete; Nyholm, Birgit et al.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 83, No. 11, 20.11.1998, p. 3992-3995.

Research output: Contribution to journal › Journal article › Research › peer-review

Urhammer, SA , Møller, AM, Nyholm, B, Ekstrøm, CT , Eiberg, H, Clausen, JO, Hansen, T , Pedersen, O & Schmitz, O 1998, 'The effect of two frequent amino acid variants of the hepatocyte nuclear factor-1α gene on estimates of the pancreatic β-cell function in Caucasian glucosetolerant first-degree relatives of type 2 diabetic patients', Journal of Clinical Endocrinology and Metabolism, vol. 83, no. 11, pp. 3992-3995.

Urhammer SA , Møller AM, Nyholm B, Ekstrøm CT , Eiberg H, Clausen JO et al. The effect of two frequent amino acid variants of the hepatocyte nuclear factor-1α gene on estimates of the pancreatic β-cell function in Caucasian glucosetolerant first-degree relatives of type 2 diabetic patients. Journal of Clinical Endocrinology and Metabolism. 1998 Nov 20;83(11):3992-3995.

Urhammer, Søren A. ; Møller, Ann Merete ; Nyholm, Birgit et al. / The effect of two frequent amino acid variants of the hepatocyte nuclear factor-1α gene on estimates of the pancreatic β-cell function in Caucasian glucosetolerant first-degree relatives of type 2 diabetic patients. In: Journal of Clinical Endocrinology and Metabolism. 1998 ; Vol. 83, No. 11. pp. 3992-3995.

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title = "The effect of two frequent amino acid variants of the hepatocyte nuclear factor-1α gene on estimates of the pancreatic β-cell function in Caucasian glucosetolerant first-degree relatives of type 2 diabetic patients",

abstract = "The objective of the present study was to investigate whether the frequent amino acid polymorphisms, Ile/Leu27 and Ser/Asn487, of the hepatocyte nuclear factor-1α gene were associated with alterations in glucose-induced serum C-peptide and serum insulin responses among glucose- tolerant first-degree relatives of type 2 diabetic patients. The study comprised 2 independent Danish cohorts. Among 74 unrelated type 2 diabetic relatives, 12 homozygous carriers of the Ile/Leu27 polymorphism had a 32% decrease in the 30-min serum C-peptide level (P = 0.01), as well as a 39% decrease in the 30-min serum insulin level (P = 0.02) during an oral glucose tolerance test. Ten homozygous carriers of the Ile/Leu27 variant did, however, not differ from wildtype carriers, with respect to the acute circulating insulin and serum C-peptide responses during an iv glucose tolerance test in the same study cohort. In a larger (more than 3-fold) study group of 230 glucose tolerant offspring of 62 type 2 diabetic probands, 33 homozygous carriers of the Ile/Leu27 variant did not differ, with respect to either serum insulin and serum C-peptide levels during an oral glucose tolerance test or acute serum insulin and serum C-peptide responses during an iv glucose tolerance test. We therefore consider the former positive finding as a statistical type I error. There were no differences in the above mentioned variables between carriers of the Ser/Asn487 polymorphism and wild- type carriers within any of the 2 study populations. Nor did carriers of combined genotypes, i.e. carriers of both the Ile/Leu27 and the Ser/Asn487 variants, show any associations with the examined variables. In conclusion, the Ile/Leu27 and Set/Ash487 polymorphisms of the hepatocyte nuclear factor- 1α gene have apparently no major impact on the pancreatic β-cell function, after an oral and iv glucose challenge, in Caucasian first-degree relatives of type 2 diabetic patients.",

author = "Urhammer, {S{\o}ren A.} and M{\o}ller, {Ann Merete} and Birgit Nyholm and Ekstr{\o}m, {Claus T.} and Hans Eiberg and Clausen, {Jesper O.} and Torben Hansen and Oluf Pedersen and Ole Schmitz",

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T1 - The effect of two frequent amino acid variants of the hepatocyte nuclear factor-1α gene on estimates of the pancreatic β-cell function in Caucasian glucosetolerant first-degree relatives of type 2 diabetic patients

AU - Urhammer, Søren A.

AU - Møller, Ann Merete

AU - Nyholm, Birgit

AU - Ekstrøm, Claus T.

AU - Eiberg, Hans

AU - Clausen, Jesper O.

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Schmitz, Ole

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Y1 - 1998/11/20

N2 - The objective of the present study was to investigate whether the frequent amino acid polymorphisms, Ile/Leu27 and Ser/Asn487, of the hepatocyte nuclear factor-1α gene were associated with alterations in glucose-induced serum C-peptide and serum insulin responses among glucose- tolerant first-degree relatives of type 2 diabetic patients. The study comprised 2 independent Danish cohorts. Among 74 unrelated type 2 diabetic relatives, 12 homozygous carriers of the Ile/Leu27 polymorphism had a 32% decrease in the 30-min serum C-peptide level (P = 0.01), as well as a 39% decrease in the 30-min serum insulin level (P = 0.02) during an oral glucose tolerance test. Ten homozygous carriers of the Ile/Leu27 variant did, however, not differ from wildtype carriers, with respect to the acute circulating insulin and serum C-peptide responses during an iv glucose tolerance test in the same study cohort. In a larger (more than 3-fold) study group of 230 glucose tolerant offspring of 62 type 2 diabetic probands, 33 homozygous carriers of the Ile/Leu27 variant did not differ, with respect to either serum insulin and serum C-peptide levels during an oral glucose tolerance test or acute serum insulin and serum C-peptide responses during an iv glucose tolerance test. We therefore consider the former positive finding as a statistical type I error. There were no differences in the above mentioned variables between carriers of the Ser/Asn487 polymorphism and wild- type carriers within any of the 2 study populations. Nor did carriers of combined genotypes, i.e. carriers of both the Ile/Leu27 and the Ser/Asn487 variants, show any associations with the examined variables. In conclusion, the Ile/Leu27 and Set/Ash487 polymorphisms of the hepatocyte nuclear factor- 1α gene have apparently no major impact on the pancreatic β-cell function, after an oral and iv glucose challenge, in Caucasian first-degree relatives of type 2 diabetic patients.

AB - The objective of the present study was to investigate whether the frequent amino acid polymorphisms, Ile/Leu27 and Ser/Asn487, of the hepatocyte nuclear factor-1α gene were associated with alterations in glucose-induced serum C-peptide and serum insulin responses among glucose- tolerant first-degree relatives of type 2 diabetic patients. The study comprised 2 independent Danish cohorts. Among 74 unrelated type 2 diabetic relatives, 12 homozygous carriers of the Ile/Leu27 polymorphism had a 32% decrease in the 30-min serum C-peptide level (P = 0.01), as well as a 39% decrease in the 30-min serum insulin level (P = 0.02) during an oral glucose tolerance test. Ten homozygous carriers of the Ile/Leu27 variant did, however, not differ from wildtype carriers, with respect to the acute circulating insulin and serum C-peptide responses during an iv glucose tolerance test in the same study cohort. In a larger (more than 3-fold) study group of 230 glucose tolerant offspring of 62 type 2 diabetic probands, 33 homozygous carriers of the Ile/Leu27 variant did not differ, with respect to either serum insulin and serum C-peptide levels during an oral glucose tolerance test or acute serum insulin and serum C-peptide responses during an iv glucose tolerance test. We therefore consider the former positive finding as a statistical type I error. There were no differences in the above mentioned variables between carriers of the Ser/Asn487 polymorphism and wild- type carriers within any of the 2 study populations. Nor did carriers of combined genotypes, i.e. carriers of both the Ile/Leu27 and the Ser/Asn487 variants, show any associations with the examined variables. In conclusion, the Ile/Leu27 and Set/Ash487 polymorphisms of the hepatocyte nuclear factor- 1α gene have apparently no major impact on the pancreatic β-cell function, after an oral and iv glucose challenge, in Caucasian first-degree relatives of type 2 diabetic patients.

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The effect of two frequent amino acid variants of the hepatocyte nuclear factor-1α gene on estimates of the pancreatic β-cell function in Caucasian glucosetolerant first-degree relatives of type 2 diabetic patients

Abstract

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